The Association Between Matrix Metalloproteinase-9 Levels in Cerebrospinal Fluid and Serum with the Severity and Outcome of Tuberculous Meningitis Patients / Hubungan Kadar Matrix Metalloproteinase-9 pada Cairan Serebrospinal dan Serum terhadap Derajat Keparahan dan Luaran Pasien Meningitis Tuberkulosis

Tuberculous meningitis (TBM) is a severe form of tuberculosis associated with high mortality and neurological morbidity. Disease severity strongly influences outcome; however, reliable biological predictors remain limited. Matrix metalloproteinase-9 (MMP-9) is a proteolytic enzyme involved in neuroinflammation and blood-brain barrier disruption, and it has been reported to be elevated in both the cerebrospinal fluid (CSF) and serum of TBM patients. This study aimed to evaluate the relationship between MMP-9 levels and the severity and outcome of TBM patients. This was an analytical observational study with a cross-sectional design involving TBM patients treated at Dr. M. Djamil General Hospital, Padang, from January to December 2024. CSF and serum MMP-9 levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Disease severity was assessed using the British Medical Research Council (BMRC) criteria, and outcomes at 14 and 60 days were assessed using the Glasgow Outcome Scale. A total of 41 TBM patients were included in the study. The mean CSF MMP-9 level was 2,034.40 ng/L, while the median serum MMP-9 level was 1,490.14 ng/L. The analysis showed no significant association between CSF MMP-9 levels and disease severity (p = 0.276), 14-day outcome (p = 0.269), or 60-day outcome (p = 0.375). Serum MMP-9 levels were likewise not associated with disease severity (p = 0.248), 14-day outcome (p = 0.224), or 60-day outcome (p = 0.138), but they still showed an increasing pattern in patients with a fatal outcome. CSF and serum MMP-9 levels had no significant association with the severity and outcome of TBM patients. These findings suggest that a single MMP-9 measurement is insufficient as a clinical predictor, so a multibiomarker and longitudinal approach should be considered.

Tuberkulosis meningitis (TBM) merupakan bentuk TB berat dengan mortalitas dan morbiditas neurologis yang tinggi. Derajat keparahan sangat memengaruhi luaran, namun prediktor biologis yang andal masih terbatas. Matrix metalloproteinase-9 (MMP-9) merupakan enzim proteolitik yang berperan dalam neuroinflamasi dan kerusakan sawar darah otak, serta dilaporkan meningkat pada cairan serebrospinal (CSS) maupun serum pasien TBM. Penelitian ini bertujuan menilai hubungan kadar MMP-9 dengan derajat keparahan dan luaran pasien TBM. Penelitian ini merupakan studi observasional analitik dengan desain cross-sectional pada pasien TBM yang dirawat di RSUP Dr. M. Djamil Padang pada bulan Januari hingga Desember 2024. Kadar MMP-9 CSS dan serum diukur menggunakan metode enzyme linked immunosorbent assay (ELISA). Derajat keparahan dinilai dengan BMRC dan luaran 14 serta 60 hari menggunakan Glasgow Outcome Scale. Terdapat sebanyak 41 pasien TBM pada penelitian. Rerata kadar MMP-9 CSS didapatkan sebesar 2.034,40 ng/L, sementara itu median kadar MMP-9 serum didapatkan sebesar 1.490,14 ng/L. Hasil analisis menunjukkan tidak terdapatnya hubungan bermakna antara kadar MMP-9 CSS dengan derajat keparahan (p = 0,276), luaran 14 hari (p = 0,269), maupun 60 hari (p = 0,375). Kadar MMP-9 serum juga tidak berhubungan dengan derajat keparahan (p = 0,248), luaran 14 hari (p = 0,224), maupun 60 hari (p = 0,138), namun tetap menunjukkan pola peningkatan pada pasien dengan luaran meninggal. Kadar MMP-9 CSS dan serum tidak memiliki hubungan yang bermakna dengan derajat keparahan dan luaran pasien TBM. Temuan ini menunjukkan bahwa MMP-9 tunggal belum cukup dijadikan prediktor klinis, sehingga pendekatan multibiomarker dan pemantauan longitudinal perlu dipertimbangkan.